crossing96/oncoscreening huggingface dataset:
Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.	OBJECTIVES: To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: We carried out a retrospective chart review of 664 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node-positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer-specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). RESULTS: Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9 years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24-2.85, P = 0.003) and cancer-specific mortality (hazard ratio 1.93, 95% confidence interval 1.14-3.25, P = 0.014). CONCLUSIONS: Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes.	bladder
Downregulation of Long Noncoding RNA LUCAT1 Suppresses the Migration and Invasion of Bladder Cancer by Targeting miR-181c-5p.	PURPOSE: The long noncoding RNA LUCAT1 (lung cancer-associated transcript 1) has been reported to be highly expressed in bladder cancer samples, but its role and molecular mechanisms need to be elucidated. METHODS: Bioinformatics methods show that miR-181c-5p is a target of LUCAT1. Here, we aimed to reveal whether LUCAT1 participates in the development of bladder cancer via targeting miR-181c-5p. The expression levels of LUCAT1 and miR-181c-5p were detected by RT-PCR technology in bladder cells and tissues. The effects of the LUCAT1/miR-181c-5p axis on cell proliferation, migration, invasion, and apoptosis were tested by CCK-8, wound healing, Transwell chambers, and flow cytometry assays. The expressions of apoptosis/migration-related proteins were detected by western blotting assays. RESULTS: The results demonstrated that LUCAT1 was overexpressed in bladder cancer tissue and cells, while miR-181c-5p showed a low expression pattern as compared to normal bladder cells and tissues. Cell proliferation, migration, and invasion capacities were significantly impaired, and cell apoptosis was enhanced when LUCAT1 was silenced in UM-UC-3 and T24 cell lines, but this effect was abolished by miR-181c-5p downregulation. In addition, miR-181c-5p downregulation impaired LUCAT1 downregulation which mediated the decreased expressions of Bcl2 and N-cadherin and the increased expressions of Bax and E-cadherin. Moreover, we found that KRAS was a direct target of miR-181c-5p and was under the positive regulation of LUCAT1. CONCLUSION: Collectively, this study reveals that knockdown of LUCAT1 inhibits the migration and invasion of bladder cancer cells in a miR-181c-5p-dependent manner, which may be related to KRAS downregulation.	bladder
Bladder Cancer and Associated Risk Factors: The African Panorama.	The African continent is unique in terms of its epidemiological evidence, causes, and possible future trends for bladder cancer (BCa). Factors include smoking rates and parasitic infection with Schistosoma haematobium. These issues in Africa could be addressed by increasing cultural awareness of BCa causes and symptoms via social media, banning smoking in public places, and ensuring that praziquantel is readily available in areas at high risk of schistosomiasis.	bladder
Decreased drug resistance of bladder cancer using phytochemicals treatment.	The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24-GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24-GCB cells in a dose-dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24-GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24-GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24-GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.	bladder
Krüppel-like factor 12 suppresses bladder cancer growth through transcriptionally inhibition of enolase 2.	Krüppel-like factors (KLFs) are transcription factors and play important roles in bladder cancer (BC). Clarifying the function of KLFs will provide new strategies for clinical treatment of BC. In this study, we found that Krüppel-like factor 12 (KLF12) was decreased in BC tissues and cells. Knockdown of KLF12 by siRNA dramatically elevated the proliferation and colony formation of BC cells. By contrast, overexpressing KLF12 suppressed the cell viability and the number of clones. Overexpression of KLF12 also regulated cell cycle progression, apoptosis and migration of BC cells. Furthermore, KLF12 bound to the promoter of enolase 2 (ENO2) and transcriptionally inhibited the expression of ENO2, which was highly expressed in BC tissues. KLF12 suppressed, while ENO2 promoted glycolysis. Lastly, ENO2 overexpression and knockdown promoted and suppressed the proliferation and migration of BC cells, respectively. These results suggest that KLF12 acts as a tumor suppressor by negatively regulated ENO2. Targeting ENO2 is a promising treatment strategy for this malignancy.	bladder
Advanced/metastatic bladder cancer: current status and future directions.	In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.	bladder
Single-Cell Sequencing-Enabled Hexokinase 2 Assay for Noninvasive Bladder Cancer Diagnosis and Screening by Detecting Rare Malignant Cells in Urine.	Bladder cancer (BC) is among the most common tumors with a high recurrence rate, necessitating noninvasive and sensitive diagnostic methods. Accurate detection of exfoliated tumor cells (ETCs) in urine is crucial for noninvasive BC diagnosis but suffers from limited sensitivity when ETCs are rare and confounded by reactive, regenerative, or reparative cells. Single-cell sequencing (SCS) enables accurate detection of ETCs by surveying oncogenic driver mutations or genome-wide copy number alternations. To overcome the low-throughput limitation of SCS, we report a SCS-validated cellular marker, hexokinase 2 (HK2), for high-throughput screening cells in urine and detecting ETCs engaging elevated glycolysis. In the SCS-based training set, a total of 385 cells from urine samples of eight urothelial carcinoma (UC) patients were sequenced to establish a HK2 threshold that achieved >90% specificity for ETC detection. This urine-based HK2 assay was tested with a blinded patient group (n = 384) including UC and benign genitourinary disorders as a validation cohort for prospectively evaluating diagnostic accuracy. The sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 90, 88, 83, and 93%, respectively, which were superior to urinary cytology. For investigating the potential to be a screening test, the HK2 assay was tested with a group of healthy individuals (n = 846) and a 6-month follow-up. The specificity was 98.4% in this health group. Three participants were found to have >5 putative ETCs that were sequenced to exhibit recurrent copy number alternations characteristic of malignant cells, demonstrating early BC detection before current clinical methods.	bladder
[Muscle invasive bladder cancer and bladder preservation protocols. Where are we?].	Radical cystectomy remains as gold standard for treatment of muscle-invasive bladder cancer. Radical cystectomy has a high morbidity and mortalityas sociated even with the new anesthetic and surgical techniques. Some patients are still not candidates for this major surgery. Besides, some patients reject radical cystectomy. Bladder preservation strategies were develop aiming to decrease morbidity and mortality related to major surgery. Bladder preservation allow for improved quality of life and similar oncologic control rates. Radical cystectomy remains as gold standard for treatment of muscle-invasive bladder cancer. Radical cystectomy has a high morbidity and mortality associated even with the new anesthetic and surgical techniques. Some patients are still not candidates for this major surgery. Besides, some patients reject radical cystectomy. Bladder preservation strategies were develop aiming to decrease morbidity and mortality related to major surgery. Bladder preservation allow for improved quality of life and similar oncologic control rates.Bladder preservation has historically been used in 2clinical scenarios: 1) Patients unable to under go a radicalcystectomy due to comorbidities o patients that rejectradical cystectomy, and 2) patients that are offeredbladder preservation strategies with and oncologicalsafety and curative intent.This is the real scenario for bladder preservation, thefirst scenario belongs to palliation, not cure.In the current manuscript, we will review the bladderpreservation strategies for muscle invasive bladdercancer, specially focusing on trimodal therapy (recommendedby international guidelines) and tetramodaltherapy.	bladder
[Epidemiology, etiology and prevention of bladder cancer.].	Bladder cancer is the seventh most frequent cancer on male population and eleventh within the whole inhabitants. Differences in incidence and mortality between countries and regions exist. Those differences depend on variables including epidemiological data, social and cultural features and economics amongst the several populations that are exposed to different risk factors and treatment approaches. Smoking is the strongest risk factor for bladder cancer, representing approximately 50% of the cases. Its alternative, the electronic cigarette does not seem to providea decrease in risk of bladder cancer. Employment exposure to aromatic amines, aromatic polycyclic hydrocarbons and chlorate hydrocarbons, are still important risk factors. Water consumption with high levels of arsenic has also shown an increased risk of bladder cancer. Fast acetylators or genetic predisposition would be tentative risk factors. Some medical treatments with chemotherapy oradiation therapy increase bladder cancer risk. Identifying all these factors allows for progress in the field of prevention and early detection. The main objective is to decrease incidence and mortality related to bladder cancer.	bladder
[Editorial: El cáncer vesical, un tumor urológico.].	Archivos Españoles de Urología finaliza el año 2020, un año difícil que todos recordaremos con tristeza como el año del Covid, editando un Número Monográfico que es pura Ciencia y Novedad ,y que también tendrá un largo recorrido en la Memoria de cuantos lo estudien o lo lean, titulado: NUEVOS PARADIGMAS EN EL CÁNCER VESICAL La importancia y relevancia del Tema seleccionado es y será notoria en tanto podemos afirmar con toda seguridad que durante 2021 y siguientes años, los artículos contenidos en el mismo, serán motivo de referencia, presentaciones, ponencias y debates en todos los foros nacionales e internacionales en los que se aborde el manejo y tratamiento del Cáncer Vesical...	bladder
Programmable N6-methyladenosine modification of CDCP1 mRNA by RCas9-methyltransferase like 3 conjugates promotes bladder cancer development.	Accumulating evidence has revealed significant roles for N6-methyladenosine (m 6 A) modification in the development of various cancers. We previously demonstrated an oncogenic role of m 6 A-modified CUB domain containing protein 1 (CDCP1) in bladder cancer (BC) progression. However, the biological functions and underlying molecular mechanisms of engineered programmable m 6 A modification of CDCP1 mRNA in BC remain obscure. Here, we established a targeted m 6 A RNA methylation system by fusing the catalytic domain of methyltransferase like 3 (METTL3CD) to RCas9 as the RNA-targeting module. The constructed RCas9- METTL3 retained methylation activity and mediated efficient site-specific m 6 A installation in the presence of a cognate single guide RNA and short protospacer adjacent motif-containing ssDNA molecule . Subsequently, targeting m 6 A installation onto the 3' untranslated region of CDCP1 promoted CDCP1 mRNA translation and facilitated BC development in vitro and in vivo. Our findings demonstrate that the RCas9-METTL3 system mediates efficient sitespecific m 6 A installation on CDCP1 mRNA and promotes BC development. Thus, the RCas9-METTL3 system provides a new tool for studying m 6 A function and a potential strategy for BC epitranscriptome-modulating therapies.	bladder
Radiation Risks for the Incidence of Kidney, Bladder and Other Urinary Tract Cancers: 1958-2009.	As part of the recent series of articles to create a comprehensive description of the radiation risks of solid cancer incidence after ionizing radiation exposure, based on the atomic bomb survivors' Life Span Study (LSS), this work focuses on the risks of urinary tract cancer (UTC) and kidney cancer. Analyses covered a 52-year period of follow-up, through 2009, among 105,444 eligible survivors who were alive and cancer free in 1958. This represents an additional 11 years of follow-up since the last comprehensive report, with a total of 3,079,502 person-years. We observed 790 UTC and 218 kidney cancer cases. Adjusted for smoking, there was a strong linear radiation dose response for UTC. The sex-averaged excess relative risk per 1 Gy (ERR/Gy) was 1.4 (95% confidence interval, CI: 0.82 to 2.1). Both males and females showed significantly increased ERRs/Gy with female point estimates at a factor of 3.4 (95% CI: 1.4 to 8.6) greater than male estimates. UTC radiation risks were largely unmodified by age at exposure or attained age. The attributable fraction of UTC to radiation exposure was approximately 18% while that attributed to smoking was 48%. Kidney cancer showed an increased ERR due to smoking (0.56 per 50 pack-years; 95% CI -0.007 to 1.6; P = 0.054), but we did not observe any strong associations of kidney cancer with radiation exposure, although sex-specific dose responses were found to be statistically different.	bladder
Bacillus Calmette-Guerin (BCG): Its fight against pathogens and cancer.	"Bacillus Calmette-Guerin (BCG) is the only FDA approved first line therapy for patients with nonmuscle invasive bladder cancer. Since the turn of the 20th century BCG has been used as a vaccine for protection against Mycobacterium tuberculosis (Mtb) and has also been found to have protection against nontuberculosis related pathogens. Recently the role of ""trained immunity"" has been identified as a possible mechanism for BCG vaccine-mediated immunity to Mtb. Similarly, BCG has been used as an immunotherapy for bladder cancer for more than 40 years, and the underlying mechanisms for BCG-mediated anti-tumor activity is poorly characterized. Several studies have shown that multiple immune pathways contribute to the immune response, and efficacy of intravesicle BCG as a cancer therapy. It is vital that we integrate our understanding of BCG as a vaccine and as a cancer therapeutic to facilitate design of future studies in order to maximize the immunotherapeutic potential of BCG. In this review we will outline the role of BCG as a vaccine, the known immune pathways that are activated by intravesical BCG and outline a potential clinical study integrating BCG vaccination prior to intravesicle instillation of BCG."	bladder
Treatment Strategies and Metabolic Pathway Regulation in Urothelial Cell Carcinoma: A Comprehensive Review.	For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) pathways, had been proven as first-line treatment for cisplatin-ineligible metastatic UC and as second-line treatment for patients with platinum-refractory metastatic UC by the U.S Food and Drug Administration (FDA). In 2020, JAVEIN bladder 100 further reported that PD-L1 inhibitors showed benefits on prolonged survival and progression-free survival as maintenance therapy. Besides targeting on immune checkpoint, manipulation of the tumor microenvironment by metabolic pathways intervention, including inhibition on tumor glycolysis, lactate accumulation and exogenous glutamine uptake, had been investigated in the past few years. In this comprehensive review, we start by introducing traditional chemotherapy of UC, and then we summarize current evidences supporting the use of immune checkpoint inhibitors and highlight ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting on metabolic pathways.	bladder
Oncologic Outcomes of Salvage Chemotherapy in Patients with Recurrent or Metastatic Lesions after Radical Nephroureterectomy: A Multi-Institutional Retrospective Study.	BACKGROUND: Radical nephroureterectomy (RNU) is the standard treatment for patients with upper tract urothelial carcinoma (UTUC). However, approximately 25% of patients experience recurrence or metastasis after RNU. This study evaluated the clinical outcome and efficacy of salvage chemotherapy (SC) after recurrence or metastasis. PATIENTS AND METHODS: Of the 441 nonmetastatic UTUC patients who underwent RNU, 147 patients with recurrent or metastatic lesions were analyzed; patients with bladder cancer recurrence were excluded. Time from disease recurrence or metastasis to cancer-specific survival (CSS) was estimated by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. RESULTS: The median time from RNU to disease recurrence or metastasis was 13.2 months. In the recurrent or metastatic sites, 31 cases (21%) were liver. In multivariate analyses, pT stage (≥pT3), time to recurrence (<12 months), and liver metastasis were independently predictive factors. In the risk stratification model for CSS after recurrence, patients were categorized into 2 groups based on pT stage, time to recurrence, and liver metastasis. The low-risk group (0-1 risk factors) included 87 patients, and the high-risk group (2-3 risk factors) included 60 patients. In the high-risk group, 27 patients received SC. The probability of CSS after recurrence or metastasis was higher in patients in the SC group compared to the non-SC group (9.5 vs. 3.7 months; p < 0.001). CONCLUSION: Two or more risk factors defined the high-risk group for patients with recurrence or metastasis after RNU. SC was associated with improved survival in patients with high-risk UTUC.	bladder
TOX-expressing terminally exhausted tumor-infiltrating CD8(+) T cells are reinvigorated by co-blockade of PD-1 and TIGIT in bladder cancer.	Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8(+) tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8(+) TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8(+) TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1(high)CD8(+) TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1(+)CD8(+) TILs. Bladder cancer patients with a high percentage of PD-1(high)TOX(+)CD8(+) TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1(+)CD8(+) TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8(+) TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8(+) TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients.	bladder